Background: Lung cancer is the leading cause of cancer death in the US. Development of novel high resolution endoscopy is essential for more accurate diagnosis, staging, and treatment of endobronchial malignancy. Recent advances in rapid acquisition high-resolution flexible fiberoptic and rigid probe optical coherence tomography (OCT) offer the potential for endoscopic real-time near histologic level optical maging to substantially advance detection, diagnostics, and treatment approaches to airway cancer. Adaptation of endoscopic OCT to airway diagnostics and therapeutics will be a major advance that requires: 1) development of 2 and 3 dimensional MEMS endoscopic probes, 2) improved acquisition times, resolution, and contrast, and 3) translational pre-clinical studies for hardware and technique optimization, and 4) clinical patient studies for demonstration of capabilities and validation of OCT for airway cancer detection. This grant proposal focuses on advancing development and clinical investigation of real-time high- resolution endoscopic OCT technology directed at specific lung cancer applications where the need for flexible and rigid high-resolution optical endoscopy is well-defined: 1) evaluation and assessment of endobronchial cancer margins, and 2) assessment of improved endobronchial cancer detection feasibility. Objectives and Aims: The overall objectives of this research proposal are to develop high resolution 3- dimensional functional OCT (F-OCT) endoscopy and evaluate its capabilities for airway early cancer detection and assessment in patients. The Specific Aims are: 1) Further the development of i) small diameter (1mm) fiberoptic, MEMS, and ii) endoscopic 3-D grid OCT probes for rigid bronchoscopy. The rigid probes will also be usable for thoracoscopy and other endoscopy applications). 2) Translate F-OCT technology to diagnosis of lung cancer and to determine OCT sensitivity and specificity capabilities for airway cancer diagnosis. 3) Combine OCT with fluorescence endoscopic technologies in clinical studies to detect bronchoscopic airway tumor with high diagnostic specificity compared to histology Study Design: Flexible fiberoptic and rigid endoscopic probe prototypes for detecting airway malignancy margins and early airway cancers will be optimized for bronchoscopic and endoscopic imaging applications in pre clinical studies, then in clinical studies to detect cancer in patients with suspected airway malignancy. Relevance: This project will develop fully functional real-time near microscopic resolution airway imaging methods and demonstrate their effectiveness in improving early airway cancer diagnosis in patients. This extension of novel engineering imaging ideas to the treatment should also enable a range of other pulmonary and non-pulmonary scope imaging applications